Substituted benzenesulfonylureas and-thioureas, processes for their preparation and use of pharmaceutical preparations based on these compounds, and medicaments containing them

ABSTRACT

This invention relates to substituted benzenesulfonylureas and -thioureas, processes for their preparation and use of pharmaceutical preparations based on these compounds, and medicaments containing them. Substituted benzenesulfonylureas and -thioureas of the formula I exhibit effects on the cardiovascular system.

This is a division of application Ser. No. 08/602,018, filed Feb. 15,1996 now U.S. Pat. No. 5,880,155.

DESCRIPTION

This invention relates to substituted benzenesulfonylureas and-thioureas, processes for their preparation and use of pharmaceuticalpreparations based on these compounds, and medicaments containing them.

The invention relates to substituted benzenesulfonylureas and -thioureasI ##STR2## in which: R(1) is hydrogen, fluorine, chlorine, alkyl having1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7carbon atoms;

R(2) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxyhaving 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4,5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbonatoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, additionally (C₁-C₈) chains in which n carbon atoms are replaced by heteroatoms, e.g. O,N or S, (where n=1-4), F or Cl;

R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbonatoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms,fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkylhaving 3, 4, 5 or 6 carbon atoms, or (C₁ -C₁₀) chains in which n carbonatoms are replaced by heteroatoms, e.g. O, N or S (n=1, 2, 3 or 4);

R(4) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms,fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkylhaving 3, 4, 5 or 6 carbon atoms, or (C₁ -C₁₀) chains in which n carbonatoms are replaced by heteroatoms, e.g. O, N or S (n=1, 2, 3 or 4); or

R(3) and R(4) together form a (CH₂)₂₋₈ ring, in which one or more of theCH₂ groups can be replaced by heteroatoms;

R(3) and R(4) can be identical or different;

E is oxygen or sulfur;

X is oxygen or sulfur;

Y is [CR(5)R(5')]_(m) ;

R(5) and R(5') independently of one another are hydrogen or alkyl having1 or 2 carbon atoms; where the members [CR(5)R(5')] are identical ordifferent;

m is 1, 2, 3 or 4;

and their pharmaceutically tolerable salts.

The term alkyl describes, if not stated otherwise, straight-chain orbranched saturated hydrocarbon radicals. The cycloalkyl radical canadditionally carry an alkyl substituent. Halogen substituents which canbe employed are the elements fluorine, chlorine, bromine and iodine.Furthermore, compounds having centers of chirality in the alkyl chainsY, R(3) and R(4) can occur. In this case, the invention includes boththe individual antipodes per se, and a mixture of the two enantiomers indifferent proportions, and also the associated meso compounds ormixtures of meso compounds, the enantiomers or diastereomers.

Similar sulfonylureas are disclosed in German Offenlegungsschrift 1 198354. The hypoglycemic actions of the sulfonylureas are describedtherein. A prototype of such hypoglycemic sulfonylureas isglibenclamide, which is used therapeutically as an agent for thetreatment of diabetes mellitus and serves in research as a much-esteemedtool for the study of so-called ATP-sensitive potassium channels. Inaddition to its hypoglycemic action, glibenclamide has still otheractions, which up to now can still not be employed therapeutically, butwhich all are attributed to blockade of exactly these ATP-sensitivepotassium channels. This includes, in particular, an antifibrillatoryaction on the heart. In the treatments of ventricular fibrillation orits preliminary stages, however, a simultaneous blood sugar fall wouldbe undesirable or even dangerous, as it can further aggravate thecondition of the patient.

It was therefore the object of the present invention to synthesizecompounds which have a cardiac action which is equally as good asglibenclamide but do not affect the blood sugar or affect it distinctlyless in cardioactive doses or concentrations than glibenclamide.

Suitable experimental animals for the detection of such actions are, forexample, mice, rats, guinea-pigs, rabbits, dogs, monkeys or pigs.

The compounds I are used as pharmaceutical active compounds in human andveterinary medicine. They can further be used as intermediates for theproduction of further pharmaceutical active compounds.

Preferred compounds I are those in which:

R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms orcycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;

R(2) is hydrogen, F, Cl, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms,alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2,3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, a (CH₂)₂₋₇chain in which one or more of the CH₂ groups can be replaced byheteroatoms O, N or S;

R(3) and R(4) are identical or different and are hydrogen, alkyl having1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms, ora (C₁ -C₁₀) chain in which one or more of the CH₂ groups can be replacedby heteroatoms O, S or N; or

R(3) and R(4) together are (CH₂)₂₋₈, in which one of the CH₂ groups canbe replaced by a heteroatom O, S or N;

E is oxygen or sulfur;

X is oxygen or sulfur;

Y is [CR(5)R(5')]_(m) ;

m is 1, 2, 3 or 4;

R(5) and R(5') independently of one another are hydrogen or alkyl having1 or 2 carbon atoms; where the members [CR(5)R(5')] are identical ordifferent;

and their pharmaceutically tolerable salts.

Particularly preferred compounds of the formula I are those in which:

R(1) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkylhaving 3, 4, 5, 6 or 7 carbon atoms;

R(2) is F, Cl, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1,2, 3 or 4 carbon atoms or a (CH₂)₂₋₇ chain, in which one or more of theCH₂ groups can be replaced by heteroatoms O, S or N;

R(3) and R(4) are identical or different and are hydrogen, alkyl having1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, cycloalkyl having 3, 4, 5or 6 carbon atoms, or (CH₂)₁₋₁₀, in which one or more CH₂ groups can bereplaced by heteroatoms O, S or N; or

R(3) and R(4) groups together (CH₂)₂₋₇, in which one of the CH₂ groupscan be replaced by heteroatoms O, S or N;

E is oxygen or sulfur;

X is oxygen or sulfur;

Y is [CR(5)R(5')]_(m) ;

R(5) and R(5') independently of one another are hydrogen or alkyl having1 or 2 carbon atoms; where the members [CR(5)R(5')] are identical ordifferent

m is 1, 2, 3 or 4;

and their pharmaceutically tolerable salts.

Very particularly preferred are those compounds I in which:

R(1) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkylhaving 3 or 4 carbon atoms;

R(2) is methoxy or ethoxy;

R(3) and R(4) are identical or different and are hydrogen, alkyl having4, 5, 6, 7 or 8 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbonatoms or a (C₃₋₈ H₇₋₁₇) group, in which one or more of the CH₂ groupscan be replaced by heteroatoms O, S or N; or

R(3) and R(4) together are the (CH₂)₂₋₈, group, in which one of the CH₂groups can be replaced by heteroatoms O, S or N;

E is sulfur or oxygen;

X is oxygen;

Y is [CR(5)R(5')]_(m) ;

R(5) and R(5') independently of one another are hydrogen or alkyl having1 or 2 carbon atoms; where the members [CR(5)R(5')] are identical ordifferent;

m is 1 or 2;

and their pharmaceutically tolerable salts.

Likewise very particularly preferred compounds I are those in which:

R(1) is hydrogen, alkyl having 1, 2 or 3 carbon atoms or cycloalkylhaving 3 carbon atoms;

R(2) is methoxy or ethoxy;

R(3) and R(4) are identical or different and are hydrogen, alkyl having5, 6, 7 or 8 carbon atoms, cycloalkyl having 5 or 6 carbon atoms or a[C₅₋₈ H₁₁₋₁₇) group, in which one or more of the CH₂ groups can bereplaced by heteroatoms O, S or N; or

R(3) and R(4) together are (CH₂)₅₋₈, in which one of the CH₂ groups canbe replaced by heteroatoms O, S or N;

E is oxgyen or sulfur;

X is oxygen;

Y is [CR(5)R(5')]_(m) ;

R(5) and R(5') independently of one another are hydrogen or alkyl having1 or 2 carbon atoms; where the members [CR(5)R(5')] are identical ordifferent;

m is 1 or 2;

and their pharmaceutically tolerable salts.

Additionally very particularly preferred compounds I are those in which:

R(1) is hydrogen, alkyl having 1, 2 or 3 carbon atoms or cycloalkylhaving 3 carbon atoms;

R(2) is methoxy or ethoxy;

R(3) is hydrogen;

R(4) is alkyl having 5, 6, 7 or 8 carbon atoms, cycloalkyl having 5 or 6carbon atoms or a (C₅₋₈ H₁₁₋₁₇) group, in which one or more of the CH₂groups can be replaced by heteroatoms O, S or N;

E is sulfur or oxygen;

X is oxygen;

Y is [CR(5)R(5')]_(m) ;

R(5) and R(5') independently of one another are hydrogen methyl; wherethe members [CR(5)R(5')] are identical or different;

m is 1 or 2;

and their pharmaceutically tolerable salts.

The compounds I of the present invention are useful pharmaceuticals forthe treatment of cardiac arrhythmias of all types of origin and for theprevention of sudden heart death due to arrhythmia and can therefore beused as antiarrhythmics. Examples of arrhythmic disorders of the heartare supraventricular arrhythmias, such as atrial tachycardias, atrialflutters or paroxysmal supraventricular arrhythmias or ventriculararrhythmias, such as ventricular extrasystoles, but in particularlife-threatening ventricular tachycardias or the particularly dangerousventricular fibrillation. They are suitable, in particular, for thosecases where arrhythmias are the consequence of a constriction of acoronary vessel, such as occur in angina pectoris or during an acutecardiac infarct or as a chronic consequence of a cardiac infarct. Theyare therefore particularly suitable in postinfarct patients for theprevention of sudden heart death. Further syndromes where arrhythmias ofthis type and/or sudden heart death due to arrhythmia play a part are,for example, cardiac insufficiency or cardiac hypertrophy as aconsequence of a chronically increased blood pressure.

Moreover, the compounds I can positively affect a decreasedcontractility of the heart. This can include a disease-related Fall incardiac contractility, for example in cardiac insufficiency, but alsoacute cases such as heart failure in the case of the effects of shock.Likewise, in the case of a heart transplantation, after operation hastaken place the heart can resume its operational capacity more rapidlyand reliably. The same applies to operations on the heart, whichnecessitate a temporary stopping of cardiac activity by means ofcardioplegic solutions, it being possible to use the compounds both forthe protection of the organs, for example during treatment with orstorage thereof in physiological bath fluids, and during transfer to therecipient body.

The invention furthermore relates to processes for the preparation ofthe compounds I. A procedure can thus be used which comprises (a)reacting a sulfonamide of the formula II ##STR3## or its salt of theformula III ##STR4## with an R(1)-substituted isocyanate of the formulaIV

    R(1)--N═C═O                                        IV

in which R(1), R(2), R(3), R(4), X, Y and M have the meanings indicatedin claim 1, to give the substituted benzenesulfonylurea Ia.

Suitable cations M in the salts of the formula III are alkali metal andalkaline earth metal ions. Equivalently to the R(1)-substitutedisocyanates IV, R(1)-substituted carbamic acid esters, R(1)-substitutedcarbamoyl halides or R(1)-substituted ureas can be employed.

(b) A benzenesulfonylurea of the formula Ia ##STR5## can be preparedfrom an aromatic benzenesulfonamide of the formula II or its salt IIIwith an R(1)-substituted trichloroacetamide of the formula V

    Cl.sub.3 C--(C═O)NH--R(1)

in the presence of a base in an inert solvent according to Synthesis1987, 734-735 at temperatures from 25° C. to 150° C.

Suitable bases are, for example, alkali metal or alkaline earth metalhydroxides, or alternatively alkoxides, such as sodium hydroxide,potassium hydroxide, calcium hydroxide, sodium methoxide, sodiumethoxide, potassium methoxide or potassium ethoxide. Suitable inertsolvents are ethers such as tetrahydrofuran, dioxane, ethylene glycoldimethyl ether (diglyme), nitriles such as acetonitrile, amides such asdimethylformamide (DMF) or N-methylpyrrolidone (NMP),hexamethylphosphoramide, sulfoxides such as DMSO, sulfones such assulfolane, hydrocarbons such as benzene, toluene, xylenes. Furthermore,mixtures of these solvents with one another are also suitable.

(c) A benzenesulfonylthiourea Ib ##STR6## is prepared from abenzenesulfonamide II or its salt III and an R(1)-substitutedisothiocyanate VI

    R(1)--N═C═S.                                       VI

(d) A benzenesulfonylurea of the formula I a can be prepared by aconversion reaction of a benzenesulfonylthiourea of the formula Ib. Thereplacement of the sulfur atom by an oxygen atom in the appropriatelysubstituted benzenesulfonylthiourea Ib can be carried out, for example,with the aid of oxides or salts of heavy metals or also by use ofoxidants such as hydrogen peroxide, sodium peroxide or nitrous acid.Thioureas can also be desulfurized by treatment with phosgene orphosphorus pentachloride. The intermediate compounds obtained arechloroformamidines or carbodiimides, which are converted into thecorresponding substituted benzenesulfonylureas Ia, for example byhydrolysis or addition of water. During desulfurization, isothioureasbehave like thioureas and can accordingly also be used as startingsubstances for these reactions.

(e) A benzenesulfonylurea Ia can be prepared by reaction of an amine ofthe formula R(1)--NH₂ with a benzenesulfonyl isocyanate of the formulaVII ##STR7##

Likewise, an amine R(1)--NH₂ can be reacted with abenzenesulfonylcarbamic acid ester, a -carbamoyl halide or abenzenesulfonylurea Ia [where R(1)=H] to give a compound I.

(f) A benzenesulfonylthiourea Ib can be prepared by reaction of an amineof the formula R(1)--NH₂ with a benzenesulfonyl isothiocyanate of theformula VllI ##STR8##

(g) A benzenesulfonylurea Ia can be prepared from a benzenesulfonylureaof the formula IX ##STR9## and R(3)R(4)NH by means of dehydrating agentsor activation by means of carbonyl halides or formation of mixedanhydrides. The dehydrating agents employed can be all compoundssuitable for the preparation of amide bonds, such asdicyclohexylcarbodiimide, carbonyldiimidazole or propanephosphoricanhydride. The solvents used are inert nonprotic solvents such as THF,DMF, diethyl ether, dichloromethane, as well as mixtures of thesesolvents.

(h) A benzenesulfonylthiourea Ib can be prepared from abenzenesulfonylthiourea of the formula X ##STR10## and R(3)R(4)NH bymeans of dehydrating agents or activation by means of carbonyl halidesor formation of mixed anhydrides. The dehydrating agents employed can beall compounds suitable for the preparation of amide bonds, such asdicyclohexylcarbodiimide, carbonyldiimidazole or propanephosphoricahydride. The solvents used are inert nonprotic solvents such as THF,DMF, diethyl ether, dichloromethane, as well as mixtures of thesesolvents.

The compounds I and their physiologically acceptable salts are usefultherapeutics which are suitable not only as antiarrhythmics, but asprophylactics in disorders of the cardiovascular system, cardiacinsufficiency, heart transplantation or cerebral vascular disorders inhumans or mammals (for example monkeys, dogs, mice, rats, rabbits,guinea-pigs and cats).

Physiologically acceptable salts of the compounds I are understoodaccording to Remmington's Pharmaceutical Science, 17th edition, 1985,pages 14-18 as meaning compounds of the formula XI, ##STR11## which canbe prepared from nontoxic organic and inorganic bases andbenzenesulfonylureas I.

Salts are preferred in this context in which M in the formula XI is asodium, potassium, rubidium, calcium or magnesium ion, and also the acidaddition products of basic amino acids, such as lysine or arginine.

The starting compounds for the mentioned synthesis processes of thebenzenesulfonylureas I are prepared by methods known per se, as aredescribed in the literature (for example in the standard works such asHouben-Weyl, Methoden der Organischen Chemie (Methods of OrganicChemistry), Georg Thieme Verlag, Stuttgart; Organic Reactions, JohnWiley & Sons, Inc., New York; and also in the patent applicationsindicated above), namely under reaction conditions which are known andsuitable for the reactions mentioned. In this case, use can also be madeof variants which are known per se but not mentioned here in moredetail. If desired, the starting substances can also be formed in situin such a way that they are not isolated from the reaction mixture, butimmediately reacted further.

A suitably substituted carboxylic acid of the formula XII can thus besubjected to a halosulfonation according to Scheme 1 and the sulfonamideXIII obtained by subsequent ammonolysis can be reacted with anappropriate amine R(3)R(4)NH after activation of the carboxylic acidgroup to give the carboxamide of the formula II. ##STR12##

Suitable activation methods are the preparation of the carbonyl chlorideor mixed carboxylic anhydrides using formyl halides. In addition, thereagents known for amide bond preparation, such as carbonyldiimidazole,dicyclohexylcarbodiimide and propanephosphoric anhydride, can be used.

The sulfonanides XIII ##STR13## obtained in Scheme 1 as intermediatescan be reacted with appropriate isocyanates of the formula

    R(1)--N═C═X

to give the benzenesulfonylureacarboxylic acids of the formula XIV##STR14##

The compounds I can have one or more chiral centers. In theirpreparation they can therefore be obtained as racemates or, if opticallyactive starting substances are used, alternatively in optically activeform. If the compounds have two or more chiral centers, they can beobtained in the synthesis as mixtures of racemates from which theindividual isomers can be isolated in pure form, for example byrecrystallizing from inert solvents. If desired, racemates obtained canbe separated into their enantiomers mechanically or chemically bymethods known per se. Diastereomers can thus be formed from theracemates by reaction with an optically active resolving agent. Suitableresolving agents for basic compounds are, for example, optically activeacids, such as the R- or R,R- and S- or S,S-forms of tartaric acid,dibenzoyltartaric acid, diacetyltartaric acid, camphorsulfonic acids,mandelic acids, malic acid or lactic acid. Carbinols can further beamidated with the aid of chiral acylating reagents, for example R- orS-α-methylbenzyl isocyanates, and then separated. The various forms ofthe diastereomers can be separated in a known morner, for example byfractional crystallization, and the enantiomers of the formula I can beliberated from the diastereomers in a known manner. Resolution ofenantiomers is further carried out by chromatography on optically activesupport materials.

The compounds I according to the invention and their physiologicallyacceptable salts can be used for the production of pharmaceuticalpreparations. In this context, they can be brought into a suitable doseform together with at least one solid or liquid excipient or auxiliaryon their own or in combination with other pharmaceuticals havingcardiovascular activity, such as calcium antagonists, NO donors or ACEinhibitors. These preparations can be used as pharmaceuticals in humanor veterinary medicine. Possible excipients are organic or inorganicsubstances which are suitable for enteral (for example oral) orparenteral administration, for example intravenous administration, ortopical applications and do not react with the novel compounds, forexample water, vegetable oils, benzyl alcohols, polyethylene glycols,glycerol triacetate, gelatin, carbohydrates such as lactose or starch,magnesium stearate, talc, lanolin and petroleum jelly. In particular,tablets, coated tablets, capsules, syrups, juices or drops are used fororal administration, solutions, preferably oily or aqueous solutions,and also suspensions, emulsions or implants, are used for rectaladministration, and ointments, creams, pastes, lotions, gels, sprays,foams, aerosols, solutions (for example in alcohols such as ethanol orisopropanol, acetonitrile, 1,2-propanediol or their mixtures with oneanother or with water) or powders are used for topical application. Thecompounds I can also be lyophilized and the lyophilizates obtained used,for example, for the production of injection preparations. In particularfor topical application, liposomal preparations are also suitable, whichcontain stabilizers and/or wetting agents, emulsifiers, salts and/orauxiliaries such as lubricants, preservatives, salts for affecting theosmotic pressure, buffer substances, colorants and flavorings and/oraromatic substances. If desired, they can also contain one or morefurther active compounds, for example one or more vitamins.

The doses which are necessary for the treatment of cardiac arrhythmiaswith the compounds I depend on whether the therapy is acute orprophylactic. Normally, a dose range of approximately at least 0.1 mg,preferably at least 1 mg, up to at most 100 mg, preferably up to at most10 mg, per kg per day is adequate if prophylaxis is conducted. The dosecan in this case be divided as an oral or parenteral individual dose orelse in up to four individual doses. If acute cases of cardiacarrhythmias are treated, for example in an intensive care unit,parenteral administration can be advantageous. A preferred dose range incritical situations can then be 10 to 100 mg and be administered, forexample, as an intravenous continuous infusion.

According to the invention, in addition to the compounds described inthe working examples, the compounds I compiled in the following Tablecan also be obtained:

(1)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methylacetamide

(2)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethylacetamide

(3)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-propylacetamide

(4)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-propylacetamide

(5)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butylacetamide

(6)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-butylacetamide

(7)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-pentylacetamide

(8)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-pentylacetamide

(9)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-pentylacetamide

(10)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butyl-2-methylacetamide

(11)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butyl-3-methylacetamide

(12)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-hexylacetamide

(13)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-hexylacetamide

(14)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-hexylacetamide

(15)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-heptylacetamide

(16)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-heptylacetamide

(17)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-heptylacetamide

(18)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-octylacetamide

(19)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-octylacetamide

(20)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-adamantylacetarmide

(21)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-adamantylacetaide

(22)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-dimethylacetamide

(23)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-ethylacetamide

(24)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-1-propylacetamide

(25)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-2-propylacetade

(26)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-1-butylacetamide

(27)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-2-butylacetamide

(28)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-diethylacetamide

(29)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethyl-N'-1-propylacetamide

(30)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethyl-N'-2-propylacetamide

(31)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylpyrrolidinylacetamide

(32)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylpiperidylacetamide

(33)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylmorpholinoacetamide

(34)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methylpiperazinylacetamide

(35)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-4-thiomorpholinylacetamide

(36)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methylacetamide

(37)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-ethylacetanmide

(38)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-propylacetamide

(39)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-propylacetamide

(40)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-butylacetamide

(41)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-butylacetamide

(42)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-pentylacetamide

(43)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-pentylacetamide

(44)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-pentylacetamide

(45)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-butyl-2-methylacetamide

(46)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-butyl-3-methylacetamide

(47)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-hexylacetamide

(48)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-hexylacetamide

(49)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-hexylacetamide

(50)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-heptylacetamide

(51)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-heptylacetamide

(52)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-heptylacetamide

(53)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-octylacetamide

(54)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide

(55)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-adamantylacetamide

(56)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-adamantylacetamide

(57)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-dimethylacetamide

(58)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methyl-N'-ethylacetamide

(59)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methyl-N'-1-propylacetamide

(60)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methyl-N'-2-propylacetamide

(61)3-Sulfanylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methyl-N'-1-butylacetamide

(62)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methyl-N'-2-butylacetamide

(63)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-diethylacetamide

(64)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-ethyl-N'-1-propylacetamide

(65)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-ethyl-N'-2-propylacetamide

(66)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylpyrrolidinylacetamide

(67)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylpiperidylacetamide

(68)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylmorpholinoacetamide

(69)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-methylpiperazinylacetamide

(70)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-4-thiomorpholinylacetamide

(71)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methylpropionamide

(72)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethylpropionamide

(73)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-propylpropionamide

(74)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-propylpropionamide

(75)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butylpropionamide

(76)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-butylpropionamide

(77)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-pentylpropionamide

(78)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-pentylpropionamide

(79)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-pentylpropionamide

(80)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butyl-2-methylpropionamide

(81)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-butyl-3-methylpropionamide

(82)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-hexylpropionamide

(83)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-hexylpropionamide

(84)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-hexylpropionamide

(85)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-heptylpropionamide

(86)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-heptylpropionamide

(87)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3-heptylpropionamide

(88)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-octylpropionamide

(89)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-octylpropionamide

(90)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-1-adamantylpropionamide

(91)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-adamantylpropionamide

(92)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-dimethylpropionamide

(93)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-ethylpropionamide

(94)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-1-propylpropionamide

(95)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-2-propylpropionamide

(96)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-1-butylpropionamide

(97)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methyl-N'-2-butylpropionamide

(98)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-diethylpropionamide

(99)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethyl-N'-1-propylpropionamide

(100)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-ethyl-N'-2-propylpropionamide

(101)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylpyrrolidinylpropionamide

(102)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylpiperidylpropionamide

(103)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenylmorpholinopropionamide

(104)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-methylpiperazinylpropionamide

(105)3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-4-thiomorpholinylpropionamide

(106)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methylpropionamide

(107)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-ethylpropionamide

(108)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-propylpropionamide

(109)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-propylpropionamide

(110)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-butylpropionamide

(111)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-butylpropionamide

(112)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-pentylpropionamide

(113)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-pentylpropionaimide

(114)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-pentylpropionamide

(115)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-butyl-2-methylpropionamide

(116)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-butyl-3-methylpropionamide

(117)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-hexylpropionamide

(118)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-hexylpropionamide

(119)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-hexylpropionamide

(120)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-heptylpropionamide

(121)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-heptylpropionamide

(122)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-3-heptylpropionamide

(123)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-octylpropionamide

(124)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-octylpropionamide

(125)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-1-adamantylpropionamide

(126)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-2-adamantylpropionamide

(127)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-dimethylpropionamide

(128)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-ethylpropionamide

(129)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-propylpropionamide

(130)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-propylpropionamide

(131)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-1-butylpropionamide

(132)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methyl-N'-2-butylpropionamide

(133)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-diethylpropionamide

(134)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-ethyl-N'-1-propylpropionamide

(135)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-ethyl-N'-2-propylpropionamide

(136)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenylpyrrolidinylpropionamide

(137)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenylpiperidylpropionamide

(138)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenylmorpholinopropionamide

(139)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-N-methylpiperazinylpropionamide

(140)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxy-phenyl-4-thiomorpholinylpropionamide

(141)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methylacetamide

(142)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-ethylacetamide

(143)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-propylacetamide

(144)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-propylacetamide

(145)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butylacetamide

(146)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-butylacetamide

(147)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-pentylacetamide

(148)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-pentylacetamide

(149)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-pentylacetamide

(150)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butyl-2-methylacetamide

(151)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butyl-3-methylacetamide

(152)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-hexylacetamide

(153)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-hexylacetamide

(154)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-hexylacetamide

(155)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-heptylacetamide

(156)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-heptylacetamide

(157)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-heptylacetamide

(158)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-octylacetamide

(159)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-octylacetamide

(160)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-adamantylacetamide

(161)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-adamantylacetamide

(162)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-dimethylacetamide

(163)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-ethylacetamide

(164)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-1-propylacetamide

(165)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-2-propylacetamide

(166)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methphenyl-N-methyl-N'-1-butylacetamide

(167)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-2-butylacetamide

(168)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-diethylacetamide

(169)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-ethyl-N'-1-propylacetamide

(170)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-ethyl-N'-2-propylacetamide

(171)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylpyrrolidinylacetamide

(172)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylpiperidylacetamide

(173)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylmorpholinoacetamide

(174)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methylpiperazinylacetamide

(175)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-4-thiomorpholinylacetamide

(176)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methylpropionamide

(177)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methylpropionamide

(178)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-propylpropionamide

(179)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-propylpropionamide

(180)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butylpropionamide

(181)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-butylpropionamide

(182)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-pentylpropionamide

(183)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-pentylpropionamide

(184)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-pentylpropionamide

(185)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butyl-2-methylpropionamide

(186)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-butyl-3-methylpropionamide

(187)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methphenyl-N-1-hexylpropionamide

(188)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-hexylpropionamide

(189)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-hexylpropionamide

(190)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methphenyl-N-1-heptylpropionamide

(191)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-heptylpropionamide

(192)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-3-heptylpropionamide

(193)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-octylpropionamide

(194)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-octylpropionamide

(195)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-1-adamantylpropionamide

(196)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-2-adamantylpropionamide

(197)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-dimethylpropionamide

(198)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-ethylpropionamide

(199)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-1-propylpropionamide

(200)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-2-propylpropionamide

(201)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-1-butylpropionamide

(202)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methyl-N'-2-butylpropionamide

(203)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-diethylpropionamide

(204)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-ethyl-N'-1-propylpropionamide

(205)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-ethyl-N'-2-propylpropionamide

(206)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylpyrrolidinylpropionamide

(207)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylpiperidylpropionamide

(208)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenylmorpholinopropionamide

(209)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-N-methylpiperazinylpropionamide

(210)3-Sulfonylamino-N-methylaminothiocarbonyl-4-methylphenyl-4-thiomorpholinylpropionamide

Preparation of the Starting Materials

Preparation of 3-Sulfonylaminophenylcarboxylic Acids

The 4-substituted phenylcarboxylic acids were added in portions withstirring to an excess of chlorosulfonic acid. The mixture was stirredfor 30 minutes at room temperature, then poured onto ice and theresulting sulfonyl chloride was filtered off with suction. The latterwas dissolved in ammonia solution, stirred at room temperature for 30minutes, and the solution was neutralized using 2N hydrochloric acid.The product obtained was filtered off with suction. Prepared accordingto this method:

3-Sulfonylamino-4-methoxyphenyl-3-propionic acid

M.p. 172-1760° C. ##STR15##

3-Sulfonylamino-4-methoxyphenylacetic acid

M.p. 1640° C. ##STR16##

3-Sulfonylamino-4-ethoxyphenylacetic acid

M.p. 183-185° C. ##STR17##

Preparation of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylacetic acid##STR18##

5 g of 3-sulfonylamino-4-methoxyphenylacetic acid were dissolved in 3 mlof DMF and stirred at 40° C. for 30 minutes with 245 mg of sodiumhydroxide. 328 mg of methyl isothiocyanate were added thereto and themixture was stirred for a further 2 h at 70° C. 2N hydrochloric acid wasadded to the cooled solution and the product was filtered off withsuction. M.p. 1740° C.

The following was prepared by an analogous procedure:

3-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-acetic acid

M.p. 152-154° C. ##STR19##

EXAMPLES Example 13-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-cyclohexylpropionamide##STR20##

500 mg of 3-sulfonylamino-4-methoxyphenyl-N-cyclohexypropionamide weredissolved in 10 ml of DMF, treated with 88 mg of NaOH and stirred at400° C. for 30 min. 107 mg of methyl isothiocyanate were then added andthe mixture was stirred at 70° C. for a further 2 h. After cooling andneutralizing with 2N hydrochloric acid, the product was filtered offwith suction and dried.

M.p. 163° C.

Example 23-Sulfonylamnno-N-methylrninothiocarbonyl-4-methoxyphenyl-N-cyclohexylacetamide##STR21##

Analogously, 360 mg of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-cyclohexylacetamidewere prepared from 500 mg of3-sulfonylamino-4-methoxyphenyl-N-cyclohexylacetamide.

M.p. 185° C.

Example 33-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-pentylacetamide##STR22##

400 mg of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylacetic acidwere dissolved in 5 ml of THF and treated with 224 mg ofcarbonyldiimidazole. The mixture was stirred at room temperature for 2h. After the addition of 120 mg of 3-aminopentane, it was stirredovernight at room temperature. The amount of solvent was reduced invacuo and the residue was added to 2N HCl. The solid was filtered offwith suction.

M.p. 169° C.

Example 43-Sulfonylamino-N-methylalminothiocarbonyl-4-methoxyphenyl-N-(R)-1-cyclohexyl-1-ethylacetamide##STR23##

Analogously to Example 3,3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-(R)-1-cyclohexyl-1-ethylacetamidewas obtained from 300 mg of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylacetic acid and144 mg of (R)-1-cyclohexyl-1-ethylamine. M.p. 84° C.

Example 53-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-(S)-1-cyclohexyl-1-ethylacetamide##STR24##

Analogously to Example 3,3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-(S)-1-cyclohexyl-1-ethylacetaimidewas obtained from 300 mg of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylacetic acid and144 mg of (S)-1-cyclohexyl-1-ethylamine.

M.p. 84° C.

Example 63-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-1-butylacetamide##STR25##

Analogously to Example 3, the product was obtained from 300 mg of3-sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenylacetic acid and83 mg of butylamine.

M.p. 136° C.

Example 73-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-isopropylpropionamide##STR26##

M.p.: 116° C.

Example 83-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-isopropylpropionamide##STR27##

M.p.: 172° C.

Example 93-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-pentylacetamide##STR28##

M.p.: 137° C.

Example 103-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-isopropylacetamide##STR29##

Oil.

Example 113-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-(R)-butylacetamide##STR30##

M.p.: 123° C.

Example 123-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-(S)-butylacetamide##STR31##

M.p.: 119° C.

Example 133-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-4-heptylacetamide##STR32##

M.p.: 118° C.

Example 143-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-6-methyl-2-heptylacetamide##STR33##

M.p.: 113° C.

Example 153-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-undecylacetamide##STR34##

Oil.

Example 163-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-hexylacetamide##STR35##

M.p.:111° C.

Example 17 3-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-3,3-dimethyl-2-butylacetamide ##STR36##

M.p.: 170° C.

Example 183-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-(S)-heptylacetamide##STR37##

M.p.: 139° C.

Example 193-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-(R)-heptylacetamide##STR38##

M.p.: 138° C.

Example 203-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR39##

M.p.: 103° C.

Example 213-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-6-2-methylheptan-2-ole-acetamide##STR40##

M.p.: 85° C.

Example 223-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-2-(S)-pentylacetamide##STR41##

M.p.: 102° C.

Example 233-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-4-heptylacetamide##STR42##

M.p.: 157° C.

Example 243-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-(S)-1-cyclohexylethylacetamide##STR43##

M.p.: 162° C.

Example 253-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-6-methyl2-heptylacetamide##STR44##

M.p.: 122° C.

Example 263-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-2-(S)-heptylacetamide##STR45##

M.p.: 137° C.

Example 273-Sulfonylamino-N-methylaminocarbonyl-4-ethoxyphenyl-N-2-(S)-heptylacetamide##STR46##

M.p.: 151° C.

Example 283-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-2-octylacetamide##STR47##

M.p.: 123° C.

Example 293-Sulfonylamino-N-methylaminothiocarbonyl-4-ethoxyphenyl-N-1-adamantylacetamide##STR48##

M.p.: 170° C.

Example 303-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyplenyl-N-n-heptylacetamide##STR49##

M.p.: 139° C.

Example 313-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-n-octylacetamide##STR50##

M.p.: 132° C.

Example 323-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-n-nonylarcetamide##STR51##

M.p.: 134° C.

Example 333-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-(S)-heptylacetamide##STR52##

M.p.: 178° C.

Example 343-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR53##

Oil

Example 351-[3-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl]-1-cyclopropane-N-2-(S)-heptylcyclopropane-1-carboxamide##STR54##

M.p.: 184° C.

Example 363-Sulfonylamino-N-ethylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR55##

M.p.: 125° C.

Example 373-Sulfonylamino-N-isopropylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR56##

M.p.: 141° C.

Example 383-Sulfonylamino-N-cyclopropylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR57##

M.p.: 128° C.

Example 393-Sulfonylamino-N-cyclohexylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR58##

Oil.

Example 403-Sulfonylamino-N-isopropylaminocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR59##

M.p.: 118° C.

Example 413-Sulfonylamino-N-cyclopropylaminocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR60##

Oil.

Example 423-Sulfonylamino-N-ethylaminocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR61##

Oil.

Example 433-Sulfonylamino-N-methylaminocarbonyl-4-ethoxyphenyl-N-2-octylacetamide##STR62##

M.p.: 78° C.

Example 443-Sulfonylamino-N-isopropylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR63##

M.p.: 141° C.

Example 453-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-4-nonylacetamide##STR64##

M.p.: 145° C.

Example 463-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-heptylacetamide##STR65##

M.p.: 100° C.

Example 473-Sulfonylamino-N-methylaminocarbonyl-4-methoxyphenyl-N-2-nonylacetamide##STR66##

M.p.: 107° C.

Example 483-Sulfonylamino-N-ethylaminothiocarbonyl-4-methoxyphenyl-N-2-(S)-heptylacetamide##STR67##

M.p.: 145° C.

Example 493-Sulfonylamino-N-isopropylaminothiocarbonyl-4-methoxhenyl-N-2-(S)-heptylacetamide##STR68##

M.p.: 159° C.

Example 503-Sulfonylamino-N-tert-butylaminothiocarbonyl-4-methoxyphenyl-N-2-octylacetamide##STR69##

M.p.: 126° C.

Example 513-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxhenyl-N-2-decylacetamide##STR70##

M.p.: 112° C.

Example 523-Sulfonylamino-N-cyclopropylaminothiocarbonyl-4-methoxyphenyl-N-2(s)-heptylacetamide##STR71##

M.p.: 165° C.

Example 533-Sulfonylamino-N-methylaminothiocarbonyl-4-propoxyphenyl-N-2-(s)-heptylacetamide##STR72##

M.p.: 120° C.

Example 543-Sulfonylamino-N-methylaminothiocarbonyl-4-methophenyl-N-4-nonylacetamide##STR73##

M.p.: 122° C.

Example 553-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-4-nonyl-2-methylacetamide##STR74##

M.p.: 136° C.

Example 563-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-4-nonyl-3-methylacetamide##STR75##

M.p.: 129° C.

Example 573-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-octyl-2,2-dimethylacetamide##STR76##

M.p.: 178° C.

Example 583-Sulfonylamino-N-methylaminothiocarbonyl-4-methoxyphenyl-N-3-octyl-2-methylacetamide##STR77##

M.p.: 123° C.

Pharmacological data:

The therapeutic properties of the compounds I can be revealed using thefollowing models:

(1) Action potential duration on the papillary muscle of the guinea-pig:

ATP deficiency states, as are observed during ischemia in the cardiacmuscle cell, lead to a reduction of the action potential duration. Theycount as one of the causes of so-called reentry arrhythmias, which cancause sudden heart death. The opening of ATP-sensitive K channels as aresult of the fall of ATP counts as causal here.

To measure the action potential, a standard micro-electrode techniquewas employed. For this, guinea-pigs of both sexes were killed by a blowto the head, the hearts were removed, and the papillary muscles wereseparated out and suspended in an organ bath. The organ bath wasirrigated with Ringer solution (0.9% NaCl, 0.048% KCl, 0.024% CaCl₂,0.02% NaHCO₃ and 0.1% glucose) and aerated with a mixture of 95% oxygenand 5% carbon dioxide at a temperature of 36° C. The muscle wasstimulated by means of an electrode using square-wave impulses of 1 Vand 1 ms duration and a frequency of 2 Hz. The action potential wasderived and recorded by means of a glass microelectrode insertedintracellularly, which was filled with 3 mM KCl solution. The substancesto be tested were added to the Ringer solution in a concentration of2.2-10⁻⁵ mol per liter. The action potential was amplified using anamplifier from Hugo Sachs and shown on an oscilloscope. The duration ofthe action potential was determined at a degree of repolarization of 95%(APD95). Action potential reductions were produced either by addition ofa 1 μM-strength solution of the potassium channel opener Hoe 234 (J.Kaiser, H. Gogelein, Naunyn-Schmiedebergs Arch. Pharm. 1991, 343, R 59)or by addition of 2-deoxyglucose. The action potential-reducing effectof these substances was prevented or reduced by the simultaneousaddition of the test substances. Test substances were added to the bathsolution as stock solutions in propanediol. The values indicated relateto measurements 30 minutes after addition. Glibenclamide was used inthese measurements as a standard. The test concentration in all cases is2×10⁻⁵ M.

The following values were measured:

    ______________________________________                                        Example No. APD95-start [ms]                                                                          APD95-30 min [ms]                                     ______________________________________                                        1           150 ± 21 157 ± 11                                           ______________________________________                                    

We claim:
 1. A benzenesulfonylurea of the formula I ##STR78## in which:R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbon atoms orcycloalkyl having 3, 4, 5, 6 or 7 carbon atoms;R(2) is hydrogen,fluorine, chlorine, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxyhaving 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4,5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbonatoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, or a (C₁ -C₈) chainin which one or more CH₂ groups can be replaced by O, NH or S; R(3) isH, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms,cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkylhaving 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5or 6 carbon atoms, or a (C₁ -C₁₀) chain in which one or more CH₂ groupscan be replaced by O, NH or S; R(4) is hydrogen, alkyl having 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5,6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6carbon atoms, fluorocycloalkyl having 3, 4, 5, or 6 carbon atoms, or a(C₁ -C₁₀) chain in which one or more CH₂ can be replaced by O, NH or S;or R(3) and R(4) together form a (CH₂)₂₋₈ ring, in which one or more ofthe CH₂ groups can be replaced by heteroatoms; E is oxygen; X is oxygenor sulfur; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independently of oneanother are hydrogen or alkyl having 1 or 2 carbon atoms; where themembers [CR(5)R(5')] are identical or different; m is 1, 2, 3, or 4;or apharmaceutically acceptable salt thereof.
 2. A compound of the formula Ior a pharmaceutically acceptable salt thereof as claimed in claim 1,wherein:R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7 carbonatoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) ishydrogen, F, Cl, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, alkoxyhaving 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxy having 1, 2, 3, 4,5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbonatoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, or a (C₂ -C₇) chainin which one to four CH₂ groups can be replaced by O, NH or S; R(3) andR(4) are identical or different and are hydrogen, alkyl having 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5,6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms, or a(C₁ -C₁₀) chain in which one to four CH₂ groups can be replaced by O, Sor NH; or R(3) and R(4) together are (CH₂)₂₋₈, in which one of the CH₂groups can be replaced by a O, S or NH; E is oxygen; X is oxygen orsulfur; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independently of oneanother are hydrogen or alkyl having 1 or 2 carbon atoms; where themembers [CR(5)R(5')] are identical or different; m is 1, 2, 3 or
 4. 3. Acompound of the formula I or a pharmaceutically acceptable salt thereofas claimed in claim 1, wherein:R(1) is hydrogen, alkyl having 1, 2, 3 or4 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2)is F, Cl, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3or 4 carbon atoms or a (C₂ -C₇) chain, in which one or more of the CH₂groups can be replaced by O, S or NH; R(3) and R(4) are identical ordifferent and are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, or a (C₁-C₁₀) chain, in which one or more CH₂ groups can be replaced by O, S orNH; or R(3) and R(4) are together (CH₂)₂₋₇, in which one of the CH₂groups can be replaced by O, S or NH; E is oxygen; X is oxygen orsulphur; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independently of oneanother are hydrogen or alkyl having 1 or 2 carbon atoms; where themembers [CR(5)R(5')] are identical or different; m is 1, 2, 3 or
 4. 4. Acompound of the formula I or a pharmaceutically acceptable salt thereofas claimed in claim 1, wherein:R(1) is hydrogen, alkyl having 1, 2, 3 or4 carbon atoms, or cycloalkyl having 3 or 4 carbon atoms; R(2) ismethoxy or ethoxy; R(3) and R(4) are identical or different and arehydrogen, alkyl having 4, 5, 6, 7 or 8 carbon atoms, cycloalkyl having3, 4, 5 or 6 carbon atoms or a (C₃ -C₈) chain, in which one or more CH₂groups can be replaced by O, S or NH; or R(3) and R(4) together are(CH₂)₂₋₈, in which one of the CH₂ groups can be replaced by O, S or NH;E is oxygen; X is oxygen; Y is [CR(5)R(5')]_(m) ;R(5) andR(5')independently of one another are hydrogen or alkyl having 1 or 2carbon atoms; where the members [CR(5)R(5')] are identical or different;m is 1 or
 2. 5. A compound of the formula I or a pharmaceuticallyacceptable salt thereof as claimed in claim 1, wherein:R(1) is hydrogen,alkyl having 1, 2 or 3 carbon atoms or cycloalkyl having 3 carbon atoms;R(2) is methoxy or ethoxy; R(3) and R(4) are identical or different andare hydrogen, alkyl having 5, 6, 7 or 8 carbon atoms, cycloalkyl having5 or 6 carbon atoms or a (C₅ -C₈) chain, in which one or more CH₂ groupscan be replaced by O, S or NH; or R(3) and R(4) together are (CH₂)₅₋₈,in which one of the CH₂ groups can be replaced by O, S or NH; E isoxygen; X is oxygen; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independentlyof one another are hydrogen or alkyl having 1 or 2 carbon atoms; wherethe members [CR(5)R(5')] are identical or different; m is 1 or
 2. 6. Acompound of the formula I or a pharmaceutically acceptable salt thereofas claimed in claim 1, wherein:R(1) is hydrogen, alkyl having 1, 2 or 3carbon atoms or cycloalkyl having 3 carbon atoms; R(2) is methoxy orethoxy; R(3) is hydrogen; R(4) is alkyl having 5, 6, 7 or 8 carbonatoms, cycloalkyl having 5 or 6 carbon atoms or a (C₅ -C₈) chain, inwhich one or more CH₂ groups can be replaced by O, S or NH; E is oxygen;X is oxygen; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independently of oneanother are hydrogen or methyl; where the members [CR(5)R(5')] areidentical or different; m is 1 or
 2. 7. A process for the preparation ofa compound of the formula I as claimed in claim 1, which comprises(a)reacting a sulfonamide of the formula II ##STR79## or its salt of theformula III ##STR80## in which M is a cation selected from the groupconsisting of alkali metal cations and alkaline earth metal cations,R(2), R(3), R(4), X and Y have the meanings indicated in claim 1, withan R(1)-substituted isocyanate of the formula IV

    R(1)--N═C═O                                        IV

in which R(1) has the meaning indicated in claim 1, to form asubstituted benzenesulfonylurea of the formula I; or (b) reacting anaromatic benzenesulfonamide of the formula II or its salt of the formulaIII with an R(1)-substituted trichloroacetamide of the formula V

    Cl.sub.3 C--(C═O)NH--R(1)

in the presence of a base to form a benzenesulfonylurea of the formulaI; or (c) reacting an amine of the formula R(1)--NH₂ with abenzenesulfonyl isocyanate of the formula VII ##STR81## to form abenzenesulfonylurea of the formula I; or (d) reacting abenzenesulfonylurea of the formula IX ##STR82## and R(3)R(4)NH in thepresence of a dehydrating agent or after activation by means of acarbonyl halide or formation of a mixed anhydride to form abenzenesulfonylurea of the formula I.
 8. A pharmaceutical compositioncomprising a benzenesulfonylurea of the formula I or a pharmaceuticallyacceptable salt thereof as claimed in claim 1, together with apharmaceutically acceptable carrier.
 9. A process for the preparation ofa compound of the formula Ia ##STR83## in which: R(1) is hydrogen, alkylhaving 1, 2, 3, 4, 5, 6 or 7 carbon atoms or cycloalkyl having 3, 4, 5,6 or 7 carbon atoms;R(2) is hydrogen, fluorine, chlorine, alkyl having1, 2, 3, 4, 5 or 6 carbon atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbonatoms, fluoroalkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms,mercaptoalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having3, 4, 5 or 6 carbon atoms, or a (C₁ -C₈) chain in which one or more CH₂groups can be replaced by O, NH or S; R(3) is H, alkyl having 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkyl having 3, 4, 5,6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6carbon atoms, fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms, or a(C₁ -C₁₀) chain in which one or more CH₂ groups can be replaced by O, NHor S; R(4) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11or 12 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbonatoms, fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms,fluorocycloalkyl having 3, 4, 5 or 6 carbon atoms, or a (C₁ -C₁₀) chainin which one or more CH₂ groups can be replaced by O, NH or S; or R(3)and R(4) together form a (CH₂)₂₋₈ ring, in which one or more of the CH₂groups can be replaced by hetero-atoms; X is oxygen or sulfur; Y is[CR(5)R(5')]_(m) R(5) and R(5') independently of one another arehydrogen or alkyl having 1 or 2 carbon atoms; where the members[CR(5)R(5')] are identical or different; m is 1, 2, 3 or 4;comprisingthe step of desulfurizing a compound of the formula Ib ##STR84##10. 10.A process for the preparation of a compound of the formula Ia as claimedin claim 9, wherein a compound of the formula Ib is reacted with anoxide or a salt of a heavy metal.
 11. A process for the preparation of acompound of the formula Ia as claimed in claim 9, wherein a compound ofthe formula Ib is reacted with an oxidant.
 12. A process for thepreparation of a compound of the formula Ia as claimed in claim 11,wherein said oxidant is selected from the group consisting of hydrogenperoxide, sodium peroxide, and nitrous acid.
 13. A process for thepreparation of a compound of the formula Ia as claimed in claim 9,wherein a compound of the formula Ib is reacted with phosgene orphosphorus pentachloride and then hydrolyzed to form said compound ofthe formula Ia.
 14. A method of investigating the inhibition ofATP-sensitive potassium channels, comprising administering an effectiveamount of a benzenesulfonylurea or benzenesulfonylthiourea of theformula I in which:R(1) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6 or 7carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms; R(2) ishydrogen, fluorine, chlorine, alkyl having 1, 2, 3, 4, 5 or 6 carbonatoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, fluoroalkoxyhaving 1, 2, 3, 4, 5 or 6 carbon atoms, mercaptoalkyl having 1, 2, 3, 4,5 or 6 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, or a(C₁ -C₈) chain in which one or more CH₂ groups can be replaced by O, NHor S; R(3) is H, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms,fluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, fluorocycloalkylhaving 3, 4, 5 or 6 carbon atoms, or a (C₁ -C₁₀) chain in which one ormore CH₂ groups can be replaced by O, NH or S; R(4) is hydrogen, alkylhaving 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 carbon atoms, cycloalkylhaving 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, fluoroalkyl having 1, 2,3, 4, 5 or 6 carbon atoms, fluorocycloalkyl having 3, 4, 5, or 6 carbonatoms, or a (C₁ -C₁₀) chain in which one or more CH₂ can be replaced byO, NH or S; or R(3) and R(4) together form a (CH₂)₂₋₈ ring, in which oneor more of the CH₂ groups can be replaced by heteroatoms; E is oxygen; Xis oxygen or sulfur; Y is [CR(5)R(5')]_(m) ;R(5) and R(5') independentlyof one another are hydrogen or alkyl having 1 or 2 carbon atoms; wherethe members [CR(5)R(5')] are identical or different; m is 1, 2, 3, or4;or a pharmaceutically acceptable salt thereof as a diagnostic agent.